PROCESS FOR PREPARATION OF (IS, 3S, 5S)-2-[(2S)-2-AMIN0-2-(3-HYDROXY-l-ADAMANTYL) ACETYL]-2-AZABICYCLO [3.1.0] HEXANE-3-CARBONITRILE

摘要

Provided are novel processes for the preparation of Saxagliptin and novel intermediates employed in the process for preparing Saxagliptin.

主权项

1. A process for the preparation of the saxagliptin comprising the steps of:
i) reacting the compound of formula Ill or its acid addition salts wherein R and R1 independently is H or C1-C6 substituted or unsubstituted alkyl group; L is a halogen or leaving group; with alkali metal azide in the presence of a phase transfer catalyst to obtain a compound of formula IV or its acid addition salts wherein R and R1 independently is H or C1-C6 substituted or unsubstituted alkyl group; ii) treating the compound of formula IV with chiral reagent to obtain the compound of formula V; iii) hydrolysis of the compound of formula V by employing mineral acid to obtain a compound of formula VI wherein R and R1 independently is H or C1-C6 substituted or unsubstituted alkyl group; iv) reacting the compound of formula VI with the compound 2-azabicyclo[3.1.0]hexane-3-carboxamide of formula VII or its acid addition salts in the presence of a coupling reagent and coupling additives to obtain a compound of formula VIII or its acid addition salts; v) dehydrating the compound of formula VIII or its acid addition salts in the presence of a dehydrating reagent and base to obtain a compound of formula IX or its acid addition salts; vi) reducing the compound of formula IX or its acid addition salts in the presence of a metal catalyst to obtain compound of formula X or its acid addition salts.